1. Field of the Invention
The present disclosure relates to a Sodium-Iodide Symporter gene optimized for the expression in eukaryotic cells and its uses.
2. Description of the Related Art
Generally in cells genes are transcribed from DNA to mRNA; which in turn are translated into proteins. During the translational process; tRNAs which carry 3 bases corresponding to each codon of a single amino acid are involved and each amino acid is encoded by more than one codon. Due to this codon degeneracy; the frequency of codon usage varies depending on the types of cells where genes are expressed. Therefore; DNA sequence is needed to be modified by synonymous nucleotide substitutions without altering the amino acid sequence of the encoded protein for the efficient expression of recombinant genes in heterologous systems.
Sodium Iodide Symporter (NIS) is a transmembrane glycoprotein with a MW of 87 kDa and 12 transmembrane domains; which transports two sodium cations for each iodide anion into cells. NIS mediated uptake of iodide into follicular cells of the thyroid gland is the first step in the synthesis of thyroid hormone resulting in 20-40 higher concentration of iodide in the thyroid.
The gene coding for NIS was first isolated in rats by Dai et al. (Dai et al.; Nature; 1996; 379: 458-460); followed by the isolation of Human NIS (hNIS) gene by Smanik et al. (Smanik et al.; Biochem. Biophysic. Res. Comm 226: 339-345; 1997).
U.S. Patent Publication 2006-0004191 relates to modified sodium iodide symporter proteins and genes for imaging and cancer therapy and discloses modified NIS proteins having a net electrostatic charge more positive than that of corresponding wild type NIS proteins.
U.S. Patent Publication 2012-0027676 relates to modified sodium iodide symporter proteins and uses thereof and discloses the modified NIS proteins in the cells results in higher intracellular levels of a substrate of a NIS protein than does the expression of the same amount of a wild-type NIS protein.
However; there exist needs to develop modified NIS genes optimized for the efficient expression in eukaryotic cells particularly in human cells for the treatment of thyroid disease and radionuclide gene therapy and molecular imaging using NIS.